Research progress of small-molecule drugs in targeting telomerase in human cancer and aging

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions Pub Date : 2023-09-01 DOI:10.1016/j.cbi.2023.110631

Ziyi Shen , Yuanhui Wang , Guanzhen Wang , Wei Gu , Shengchao Zhao , Xiaomeng Hu , Wei Liu , Yi Cai , Zhihong Ma , Rupesh K. Gautam , Jia Jia , Chunpeng (Craig) Wan , Tingdong Yan

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Abstract

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.

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端粒酶靶向小分子药物在人类癌症和衰老中的研究进展

端粒是位于线性染色体末端的独特结构，负责稳定染色体结构。它们由端粒酶合成，端粒酶是一种逆转录酶核糖核蛋白复合物。除了干细胞和生殖细胞外，人类体细胞通常没有端粒酶活性。每次细胞分裂时，端粒序列都会缩短，当端粒达到临界极限时，最终导致复制性衰老和细胞凋亡。然而，大多数人类癌细胞表现出增加的端粒酶活性，使它们能够持续分裂。端粒酶在癌症和衰老中的重要性使得开发针对端粒酶的药物成为研究的焦点。这些药物可以通过提高端粒相关综合征或疾病的端粒酶活性来抑制癌细胞生长和延缓衰老。本文综述了端粒、端粒酶及其在癌症和衰老中的调控作用，并重点介绍了针对端粒酶的小分子药物在这些领域的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemico-Biological Interactions 生物-毒理学

CiteScore

7.70

自引率

3.90%

发文量

410

审稿时长

36 days

期刊介绍： Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.